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Recruiting NCT02965326

Surrogate Markers of Response to New Therapies in Cystic Fibrosis Patients

No phase Interventional Cystic Fibrosis

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Nasal swab; rectal biopsy..
Who it may be relevant to
Registry conditions: Cystic Fibrosis. Basic parameters: No limits · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
France
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Personalized Therapy of Cystic Fibrosis: Set-up of Response Markers

Overview

The purpose of this study is to determine which biological marker, or association of biological markers, best predict clinical response of cystic fibrosis patients to CFTR modulators.

Detailed description

This study is based upon the hypothesis that clinical response of cystic fibrosis patients to CFTR modulators is correlated to in vitro responses to these drugs of epithelial cells derived from the patients, as assessed by CFTR-dependent Chloride secretion. Epithelial cells will be derived either from nasal or rectal epithelia, and consist both of cultured cells and organoids. The drugs tested will be Ivacaftor, or Lumacaftor/Ivacaftor, according to patient's treatment. Results of these assays will be compared with response to treatment at 6 and 12 months, assessed by clinical response and in vivo assay of CFTR function.

Interventions

  • Procedure Nasal swab; rectal biopsy.
    Nasal epithelial cells will be obtained by nasal swabs from patients of the three arms; intestinal epithelial cells will be obtained, by rectal biopsy, only from patients treated by CFTR modulators.

Primary outcome measures

  • Forced Expiratory Volume in 1 second [Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months]
Secondary outcome measures (12)
  • Forced Vital Capacity [Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months]
  • Forced Expiratory Flow 25-75 [Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months]
  • Residual Volume [Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months]
  • elastase in sputum [Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months]
  • calprotectin in sputum [Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months]
  • IL-8 in sputum [Time frame: initiation, 7 days, 1 month, 6 months, 1 year and every 6 months]
  • Calprotectin in blood [Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months]
  • IL-8 in blood [Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months]
  • tumor necrosis factor in sputum [Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months]
  • liver function test in blood [Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months]
  • liver function test/SGPT in blood [Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months]
  • liver function test/bilirubin in blood [Time frame: initiation, 1 month, 3 Months, 6 months and every 6 months]

Eligibility criteria

Inclusion criteria

  • Cystic fibrosis patients treated by CFTR modulators (Ivacaftor or the association Ivacaftor-Lumacaftor)
  • Cystic fibrosis patients non treated by CFTR modulators
  • Patients in whom cystic fibrosis diagnosis has been suspected, but excluded by physiological and genetic investigations

Exclusion criteria

  • pregnant or lactating women
  • contraindication to nasal swab
  • contraindication to rectal biopsy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Basic science

Study locations

France · 1 center
  • Necker Hospital — Paris

Publications

  • Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordonez C, Elborn JS; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185. PMID 22047557
  • Graeber SY, Hug MJ, Sommerburg O, Hirtz S, Hentschel J, Heinzmann A, Dopfer C, Schulz A, Mainz JG, Tummler B, Mall MA. Intestinal Current Measurements Detect Activation of Mutant CFTR in Patients with Cystic Fibrosis with the G551D Mutation Treated with Ivacaftor. Am J Respir Crit Care Med. 2015 Nov 15;192(10):1252-5. doi: 10.1164/rccm.201507-1271LE. No abstract available. PMID 26568242
  • Quittner A, Suthoff E, Rendas-Baum R, Bayliss MS, Sermet-Gaudelus I, Castiglione B, Vera-Llonch M. Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial. Health Qual Life Outcomes. 2015 Jul 2;13:93. doi: 10.1186/s12955-015-0293-6. PMID 26135562
  • De Boeck K, Munck A, Walker S, Faro A, Hiatt P, Gilmartin G, Higgins M. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros. 2014 Dec;13(6):674-80. doi: 10.1016/j.jcf.2014.09.005. Epub 2014 Sep 26. PMID 25266159
  • Boyle MP, Bell SC, Konstan MW, McColley SA, Rowe SM, Rietschel E, Huang X, Waltz D, Patel NR, Rodman D; VX09-809-102 study group. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38. doi: 10.1016/S2213-2600(14)70132-8. Epub 2 PMID 24973281
  • Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220-31. doi: 10.1056/NEJMoa14095 PMID 25981758
  • De Boeck K, Kent L, Davies J, Derichs N, Amaral M, Rowe SM, Middleton P, de Jonge H, Bronsveld I, Wilschanski M, Melotti P, Danner-Boucher I, Boerner S, Fajac I, Southern K, de Nooijer RA, Bot A, de Rijke Y, de Wachter E, Leal T, Vermeulen F, Hug MJ, Rault G, Nguyen-Khoa T, Barreto C, Proesmans M, Sermet-Gaudelus I; European Cystic Fibrosis Society Clinical Trial Network Standardisation Committee. PMID 22878883
  • Dekkers JF, Wiegerinck CL, de Jonge HR, Bronsveld I, Janssens HM, de Winter-de Groot KM, Brandsma AM, de Jong NW, Bijvelds MJ, Scholte BJ, Nieuwenhuis EE, van den Brink S, Clevers H, van der Ent CK, Middendorp S, Beekman JM. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med. 2013 Jul;19(7):939-45. doi: 10.1038/nm.3201. Epub 2013 Jun 2. PMID 23727931

Identifiers

NCT: NCT02965326 · ABCF-2016-01 · 2016-A00309-42

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗